Effect of acute physiological free fatty acid elevation in the context of hyperinsulinemia on fiber type-specific IMCL accumulation.

It is well described that increasing free fatty acids (FFAs) to high physiological levels reduces insulin sensitivity. In sedentary humans, intramyocellular lipid (IMCL) is inversely related to insulin sensitivity. Since muscle fiber composition affects muscle metabolism, whether FFAs induce IMCL accumulation in a fiber type-specific manner remains unknown. We hypothesized that in the setting of acute FFA elevation by lipid infusion within the context of a hyperinsulinemic-euglycemic clamp, IMCL will preferentially accumulate in type 1 fibers. Normal-weight participants (n = 57, mean ± SE: age 24 ± 0.6 yr, BMI 22.2 ± 0.3 kg/m(2)) who were either endurance trained or sedentary by self-report were recruited from the University of Minnesota (n = 31, n = 15 trained) and University of Pittsburgh (n = 26, n = 14 trained). All participants underwent a hyperinsulinemic-euglycemic clamp in the context of a 6-h infusion of either lipid or glycerol control. A vastus lateralis muscle biopsy was obtained at baseline and end-infusion (6 h). The muscle biopsies were processed and analyzed at the University of Pittsburgh for fiber type-specific IMCL accumulation by Oil-Red-O staining. Regardless of training status, acute elevation of FFAs to high physiological levels (~400-600 meq/l) increased IMCL preferentially in type 1 fibers (+35 ± 11% compared with baseline, +29 ± 11% compared with glycerol control: P < 0.05). The increase in IMCL correlated with a decline in insulin sensitivity as measured by the hyperinsulinemic-euglycemic clamp (r = -0.32, P < 0.01) independent of training status. Regardless of training status, increase of FFAs to a physiological range within the context of hyperinsulinemia shows preferential IMCL accumulation in type 1 fibers.NEW & NOTEWORTHY This novel human study examined the effects of FFA elevation in the setting of hyperinsulinemia on accumulation of fat in specific types of muscle fibers. Within the context of the hyperinsulinemic-euglycemic clamp, we found that an increase of FFAs to a physiological range sufficient to reduce insulin sensitivity is associated with preferential IMCL accumulation in type 1 fibers

Skeletal muscle as a regulator of the longevity protein, Klotho

Klotho is a powerful longevity protein that has been linked to the prevention of muscle atrophy, osteopenia, and cardiovascular disease. Similar anti-aging effects have also been ascribed to exercise and physical activity. While an association between muscle function and Klotho expression has been previously suggested from longitudinal cohort studies, a direct relationship between circulating Klotho and skeletal muscle has not been investigated. In this paper, we present a review of the literature and preliminary evidence that, together, suggests Klotho expression may be modulated by skeletal muscle activity. Our pilot clinical findings performed in young and aged individuals suggest that circulating Klotho levels are upregulated in response to an acute exercise bout, but that the response may be dependent on fitness level. A similar upregulation of circulating Klotho is also observed in response to an acute exercise in young and old mice, suggesting that this may be a good model for mechanistically probing the role of physical activity on Klotho expression. Finally, we highlight overlapping signaling pathways that are modulated by both Klotho and skeletal muscle and propose potential mechanisms for cross-talk between the two. It is hoped that this review will stimulate further consideration of the relationship between skeletal muscle activity and Klotho expression, potentially leading to important insights into the well-documented systemic anti-aging effects of exercise. © 2014 Avin, Coen, Huang, Stolz, Sowa, Dubé, Goodpaster, O'Doherty and Ambrosio

'Designer atoms' for quantum metrology

Entanglement is recognized as a key resource for quantum computation and quantum cryptography. For quantum metrology, the use of entangled states has been discussed and demonstrated as a means of improving the signal-to-noise ratio. In addition, entangled states have been used in experiments for efficient quantum state detection and for the measurement of scattering lengths. In quantum information processing, manipulation of individual quantum bits allows for the tailored design of specific states that are insensitive to the detrimental influences of an environment. Such 'decoherence-free subspaces' protect quantum information and yield significantly enhanced coherence times. Here we use a decoherence-free subspace with specifically designed entangled states to demonstrate precision spectroscopy of a pair of trapped Ca+ ions; we obtain the electric quadrupole moment, which is of use for frequency standard applications. We find that entangled states are not only useful for enhancing the signal-to-noise ratio in frequency measurements - a suitably designed pair of atoms also allows clock measurements in the presence of strong technical noise. Our technique makes explicit use of non-locality as an entanglement property and provides an approach for 'designed' quantum metrology

Calcium ion currents mediating oocyte maturation events

During maturation, the last phase of oogenesis, the oocyte undergoes several changes which prepare it to be ovulated and fertilized. Immature oocytes are arrested in the first meiotic process prophase, that is morphologically identified by a germinal vesicle. The removal of the first meiotic block marks the initiation of maturation. Although a large number of molecules are involved in complex sequences of events, there is evidence that a calcium increase plays a pivotal role in meiosis re-initiation. It is well established that, during this process, calcium is released from the intracellular stores, whereas less is known on the role of external calcium entering the cell through the plasma membrane ion channels. This review is focused on the functional role of calcium currents during oocyte maturation in all the species, from invertebrates to mammals. The emerging role of specific L-type calcium channels will be discussed

Exploring Pathways for Building Trust in Vaccination and Strengthening Health System Resilience

Background: Trust is critical to generate and maintain demand for vaccines in low and middle income countries. However, there is little documentation on how health system insufficiencies affect trust in vaccination and the process of re-building trust once it has been compromised. We reflect on how disruptions to immunizations systems can affect trust in vaccination and can compromise vaccine utilization. We then explore key pathways for overcoming system vulnerabilities in order to restore trust, to strengthen the resilience of health systems and communities, and to promote vaccine utilization. Methods: Utilizing secondary data and a review of the literature, we developed a causal loop diagram (CLD) to map the determinants of building trust in immunizations. Using the CLD, we devised three scenarios to illustrate common vulnerabilities that compromise trust and pathways to strengthen trust and utilization of vaccines, specifically looking at weak health systems, harmful communication channels, and role of social capital. Spill-over effects, interactions and other dynamics in the CLD were then examined to assess leverage points to counter these vulnerabilities. Results: Trust in vaccination arises from the interactions among experiences with the health system, the various forms of communication and social capital – both external and internal to communities. When experiencing system-wide shocks such as the case in Ebola-affected countries, distrust is reinforced by feedback between the health and immunization systems where distrust often lingers even after systems are restored and spills over beyond vaccination in the broader health system. Vaccine myths or anti-vaccine movements reinforce distrust. Social capital – the collective value of social networks of community members – plays a central role in increasing levels of trust. Conclusions: Trust is important, yet underexplored, in the context of vaccine utilization. Using a CLD to illustrate various scenarios helped to explore how common health and vaccine vulnerabilities can reinforce and spill over distrust through vicious, reinforcing feedback. Restoring trust requires a careful balance between eliminating vulnerabilities and strengthening social capital and interactions among communication channels

Development and psychometric properties of a belief-based Physical Activity Questionnaire for Diabetic Patients (PAQ-DP)

<p>Abstract</p> <p>Background</p> <p>This study carried out to develop a scale for assessing diabetic patients' perceptions about physical activity and to test its psychometric properties (The Physical Activity Questionnaire for Diabetic Patients-PAQ-DP).</p> <p>Methods</p> <p>An item pool extracted from the Theory of Planned Behavior literature was generated. Then an expert panel evaluated the items by assessing content validity index and content validity ratio. Consequently exploratory factor analysis (EFA) was performed to indicate the scale constructs. In addition reliability analyses including internal consistency and test-retest analysis were carried out.</p> <p>Results</p> <p>In all a sample of 127 women with diabetes participated in the study. Twenty-two items were initially extracted from the literature. A six-factor solution (containing 19 items) emerged as a result of an exploratory factor analysis namely: instrumental attitude, subjective norm, perceived behavioral control, affective attitude, self-identity, and intention explaining 60.30% of the variance observed. Additional analyses indicated satisfactory results for internal consistency (Cronbach's alpha ranging from 0.54 to 0.8) and intraclass correlation coefficients (ranging from 0.40 to 0.92).</p> <p>Conclusions</p> <p>The Physical Activity Questionnaire for Diabetic Patients (PAQ-DP) is the first instrument that applies the Theory of Planned Behavior in its constructs. The findings indicated that the PAQ-DP is a reliable and valid measure for assessing physical activity perceptions and now is available and can be used in future studies.</p

Hospitalisation with Infection, Asthma and Allergy in Kawasaki Disease Patients and Their Families: Genealogical Analysis Using Linked Population Data

Background: Kawasaki disease results from an abnormal immunological response to one or more infectious triggers. We hypothesised that heritable differences in immune responses in Kawasaki disease-affected children and their families would result in different epidemiological patterns of other immune-related conditions. We investigated whether hospitalisation for infection and asthma/allergy were different in Kawasaki disease-affected children and their relatives. Methods/Major Findings: We used Western Australian population-linked health data from live births (1970-2006) to compare patterns of hospital admissions in Kawasaki disease cases, age- and sex-matched controls, and their relatives. There were 295 Kawasaki disease cases and 598 age- and sex-matched controls, with 1,636 and 3,780 relatives, respectively. Compared to controls, cases were more likely to have been admitted at least once with an infection (cases, 150 admissions (50.8%) vs controls, 210 admissions (35.1%); odds ratio (OR) = 1.9, 95% confidence interval (CI) 1.4-2.6, P = 7.2×10-6), and with asthma/allergy (cases, 49 admissions (16.6%) vs controls, 42 admissions (7.0%); OR = 2.6, 95% CI 1.7-4.2, P = 1.3×10-5). Cases also had more admissions per person with infection (cases, median 2 admissions, 95% CI 1-5, vs controls, median 1 admission, 95% CI 1-4, P = 1.09×10-5). The risk of admission with infection was higher in the first degree relatives of Kawasaki disease cases compared to those of controls, but the differences were not significant. Conclusion: Differences in the immune phenotype of children who develop Kawasaki disease may influence the severity of other immune-related conditions, with some similar patterns observed in relatives. These data suggest the influence of shared heritable factors in these families

The development, design, testing, refinement, simulation and application of an evaluation framework for communities of practice and social-professional networks

Background. Communities of practice and social-professional networks are generally considered to enhance workplace experience and enable organizational success. However, despite the remarkable growth in interest in the role of collaborating structures in a range of industries, there is a paucity of empirical research to support this view. Nor is there a convincing model for their systematic evaluation, despite the significant potential benefits in answering the core question: how well do groups of professionals work together and how could they be organised to work together more effectively? This research project will produce a rigorous evaluation methodology and deliver supporting tools for the benefit of researchers, policymakers, practitioners and consumers within the health system and other sectors. Given the prevalence and importance of communities of practice and social networks, and the extent of investments in them, this project represents a scientific innovation of national and international significance. Methods and design. Working in four conceptual phases the project will employ a combination of qualitative and quantitative methods to develop, design, field-test, refine and finalise an evaluation framework. Once available the framework will be used to evaluate simulated, and then later existing, health care communities of practice and social-professional networks to assess their effectiveness in achieving desired outcomes. Peak stakeholder groups have agreed to involve a wide range of members and participant organisations, and will facilitate access to various policy, managerial and clinical networks. Discussion. Given its scope and size, the project represents a valuable opportunity to achieve breakthroughs at two levels; firstly, by introducing novel and innovative aims and methods into the social research process and, secondly, through the resulting evaluation framework and tools. We anticipate valuable outcomes in the improved understanding of organisational performance and delivery of care. The project's wider appeal lies in transferring this understanding to other health jurisdictions and to other industries and sectors, both nationally and internationally. This means not merely publishing the results, but contextually interpreting them, and translating them to advance the knowledge base and enable widespread institutional and organisational application

A web-based Alcohol Clinical Training (ACT) curriculum: Is in-person faculty development necessary to affect teaching?

<p>Abstract</p> <p>Background</p> <p>Physicians receive little education about unhealthy alcohol use and as a result patients often do not receive efficacious interventions. The objective of this study is to evaluate whether a free web-based alcohol curriculum would be used by physician educators and whether in-person faculty development would increase its use, confidence in teaching and teaching itself.</p> <p>Methods</p> <p>Subjects were physician educators who applied to attend a workshop on the use of a web-based curriculum about alcohol screening and brief intervention and cross-cultural efficacy. All physicians were provided the curriculum web address. Intervention subjects attended a 3-hour workshop including demonstration of the website, modeling of teaching, and development of a plan for using the curriculum. All subjects completed a survey prior to and 3 months after the workshop.</p> <p>Results</p> <p>Of 20 intervention and 13 control subjects, 19 (95%) and 10 (77%), respectively, completed follow-up. Compared to controls, intervention subjects had greater increases in confidence in teaching alcohol screening, and in the frequency of two teaching practices – teaching about screening and eliciting patient health beliefs. Teaching confidence and teaching practices improved significantly in 9 of 10 comparisons for intervention, and in 0 comparisons for control subjects. At follow-up 79% of intervention but only 50% of control subjects reported using any part of the curriculum (p = 0.20).</p> <p>Conclusion</p> <p>In-person training for physician educators on the use of a web-based alcohol curriculum can increase teaching confidence and practices. Although the web is frequently used for disemination, in-person training may be preferable to effect widespread teaching of clinical skills like alcohol screening and brief intervention.</p

Internal medicine residency training for unhealthy alcohol and other drug use: recommendations for curriculum design

<p>Abstract</p> <p>Background</p> <p>Unhealthy substance use is the spectrum from use that risks harm, to use associated with problems, to the diagnosable conditions of substance abuse and dependence, often referred to as substance abuse disorders. Despite the prevalence and impact of unhealthy substance use, medical education in this area remains lacking, not providing physicians with the necessary expertise to effectively address one of the most common and costly health conditions. Medical educators have begun to address the need for physician training in unhealthy substance use, and formal curricula have been developed and evaluated, though broad integration into busy residency curricula remains a challenge.</p> <p>Discussion</p> <p>We review the development of unhealthy substance use related competencies, and describe a curriculum in unhealthy substance use that integrates these competencies into internal medicine resident physician training. We outline strategies to facilitate adoption of such curricula by the residency programs. This paper provides an outline for the actual implementation of the curriculum within the structure of a training program, with examples using common teaching venues. We describe and link the content to the core competencies mandated by the Accreditation Council for Graduate Medical Education, the formal accrediting body for residency training programs in the United States. Specific topics are recommended, with suggestions on how to integrate such teaching into existing internal medicine residency training program curricula.</p> <p>Summary</p> <p>Given the burden of disease and effective interventions available that can be delivered by internal medicine physicians, teaching about unhealthy substance use must be incorporated into internal medicine residency training, and can be done within existing teaching venues.</p